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ABSTRACT
Erythema multiforme is an autoimmune condition that can affect the skin and mucosa. Oral lesions initially
present with edema and progress to superficial erosions with pseudomembrane formation. The most rec-
ommended treatment is the use of corticosteroids; however, low-level laser therapy can be effective in the
treatment of erythema multiforme. We report a case of erythema multiforme in the oral mucosa treated
with low-level laser therapy. A 73-year-old woman using alendronate for osteoporosis, losartan, and puran
T4 with extensive ulcers on the upper and lower lips. The clinical diagnosis was erythema multiforme. The
proposed treatment was 0.05% clobetasol propionate in gel, 3 times a day, and seven sessions of low-level
laser therapy on alternate days. Low-level laser therapy significantly improved the erythema multiforme of
the oral mucosa, offering the patient a non-invasive approach with no side effects.
Key words: erythema multiforme, treatment, low-level laser therapy, photobiomodulation, laser.
Low-level laser therapy as an adjuvant in the treatment of erythema multiforme
of the oral mucosa: a case report
Thayná Melo de Lima Morais,
1
Sara Maria Santos Dias da Silva,
1
Felipe da Silva Peralta,
2
Dárcio Kitakawa,
3
Marcelo Saito Nogueira,
4
Luis Felipe das Chagas e Silva de Carvalho
1,5
1
Dentistry Department, University of Taubate, Taubaté, Brazil;
2
UNISOCIESC - Universidade Sociedade Educacional de Santa Catarina,
Joinveille - SC, Brazil;
3
CK Estomatologia, São Paulo, Brazil;
4
Tyndal University, Cork, Irlanda;
5
Dentistry Department,
University Center of Braz Cubas, Mogi das Cruzes, Brazil
Corresponding author:
Thayná Melo de Lima Morais, Ph.D, Private service, CK estomatologia,
Rua Catulo da paixão cearense, Vila Saúde, São Paulo/SP, Brazil, Postal code: 04145-010.
E-mail address: moraistml@gmail.com
Laser Therapy
©
Copyright: the Author(s), 2024
Licensee PAGEPress, Italy
Laser Therapy 2024; 31:386
doi:10.4081/ltj.2024.386
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
20
Received: 16 January 2024.
Accepted: 5 February 2024.
Non-commercial use only
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Volume 31 - N. 1
Laser Therapy 21
Introduction
Erythema multiforme (EM) is an immune-mediated
condition that can involve skin and mucous
membranes.
1
Classically, the lesions present as ulcers and
blisters that are characterized by target lesions symmet-
rically distributed on the extremities and trunk.
2,3
Ho-
wever, EM can be seen in dentistry, and the onset of the
condition results in the need for immediate diagnosis
and care.
3
EM has a wide spectrum of clinical and his-
tological manifestations, which has led to controversy
over the distinction between EM, Steven Johnson syn-
drome, and toxic epidermal necrolysis.
4-9
Thus, oral le-
sions resulting from systemic diseases represent a very
large clinical challenge in terms of therapy, mainly due
to the relationship with autoimmune diseases that re-
quire treatment based on corticotherapy, which can
cause several side effects to the patient.
Low-level laser therapy (LLLT) was discovered in 1967
by Endre Mester at Semmelweis Medical University in
Hungary.
7
Since those days, photobiomodulation
(PBM) has made and continues to make, great strides in
understanding the mechanisms of action at the molecu-
lar, cellular, and tissue levels.
10
Thus, many diseases, con-
ditions, and therapeutic fields are becoming amenable
to the beneficial effects of PBM.
7
So, LLLT is a very valid option for the treatment of oral
lesions associated with many of these pathologies, such
as lichen planus, pemphigus vulgaris, erythema multi-
forme, and aphthous ulcers. Among the benefits of laser
therapy, we can mention the ease of application by the
professional, and the almost absence of side effects from
the use of laser, we emphasize that an adequate treatment
plan can be extremely effective for the treatment of the
patient and improvement of signs and symptoms. In the
present study, we aim to report a clinical case of ery-
thema multiforme with extensive lesions on the lip,
which was fully controlled with the use of low-level laser
therapy associated with high-potency topical corticoste-
roids.
8,9
Case Report
A 73-year-old female patient sought the stomatology
service complaining of an ulcerated lesion with painful
symptoms in the upper and lower lips. Evolution time
of 1 year. During this time, the patient sought other den-
tists, but no proposed treatment was effective. Past dental
history revealed that a previous incisional biopsy had
been performed and the histopathological medical report
was actinic cheilitis. Treatment with imiquimod, 250
mg, was unsuccessful. Past medical history revealed
weekly use of alendronate for osteoporosis, losartan, and
puran T4. Investigation for harmful habits was carried
out, but nothing of note was observed. In the intraoral
examination, he observed extensive ulcers on the upper
and lower labial mucosa, which caused bleeding and a
lot of pain (Figure 1). The clinical hypothesis was ery-
thema multiforme. The proposed treatment was the use
of 0.05% clobetasol propionate in gel, 3 times a day, and
seven PBM sessions on alternate days. The device used
for PBM was THEPAPY XT with wavelength in the red
range (660nm), power of 40mw, energy density of
60J/cm2, and application time of 20 seconds per point.
Infrared band of 880nm, power of 10mw, density of
60J/cm2, application time of 20 seconds per point. The
patient improved significantly with the use of topical
corticosteroids and LLLT applications (Figure 1).
Discussion
EM is an autoimmune disease that can affect the skin
and mucosa.
1
Mucosal lesions can cause prodromic
weakness, fever, and malaise.
11,12
Although the oral cav-
ity is the most affected, oral lesions can be extremely
painful.
1
As for the etiology, infections are associated in
most cases, mainly those caused by herpes simplex virus
(HSV) type 1 and HSV type 2. Drugs such as non-ste-
roidal anti-inflammatory drugs, antiepileptic drugs, and
antibiotics can cause EM. The antibiotics sulfonamide,
penicillin, erythromycin, nitrofurantoin, and tetracycline
are the most linked to the development of EM.
3
Other
etiologic factors can cause EM; however, the incidence
is low.
1,11,13
In the present case, the patient used some
routine medications, but no medication is part of the
risk group for the development of EM, and we had no
information about other possible etiological causes.
Clinically, EM on the skin starts as pink or red papules,
which can turn into plaques that can cause burning or
itching. In the first five days, the EM can take on a dif-
ferent appearance. The inveterate lesion of erythema
multiforme is called target or iris lesion. It is a round le-
sion of three concentric segments: a dark center, sur-
rounded by a lighter pink ring, both surrounded by a
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Laser Therapy22
red ring.
1-3
While mucous membrane EM usually in-
volves the labial mucosa, buccal mucosa, free gingiva,
and lip vermilion. The initial clinical feature is erythema
with edema and progresses to superficial erosions with
pseudomembrane formation
11-13
which corroborates the
history and the clinical findings of this case. However,
mucosal EM involvement can vary in severity.
Treatment for oral mucosal MS may vary in the degree
of involvement. Patients with minimal involvement can
be treated with high-potency topical corticosteroids
while patients with more debilitating involvement can
be treated with systemic corticosteroids (i.e., prednisone
40-60 mg/d with drug weaning over 2-4 weeks).
12,14
Al-
though corticosteroids are the most frequent approach
in the treatment of EM, our patient was first treated by
another healthcare professional with an immune re-
sponse modulator, imiquimod, without success. Thus,
after our evaluation and diagnosis, topical corticosteroid
and LLLT were performed.
Photobiomodulation therapy, in recent years, has
played an influence on in vitro and in vivo studies re-
lated to oral medicine. Because PBM is based on the
interaction of photochemical mechanism and intracel-
lular mitochondrial chromophores that are light-absor-
bing molecules, laser energy is converted into metabolic
energy by the respiratory chain with the production of
adenosine triphosphate (ATP).
14,15
Thus, a cascade of
reactions is activated allowing: i) acceleration of elec-
tron transfers in the respiratory chain attributed to
changes in redox properties;
16
ii) conversion of energy
into heat, defining the rise in temperature of the chro-
mophore in a transient way;
16
iii) singlet oxygen;
16
iv)
Figure 1. Initial clinical feature and follow-up. A) Initial clinical appearance, ulcerated lesion in vermilion of upper and lower lips; B) clinical feature
after the third photobiomodulation session; C) clinical appearance after the 5
th
photobiomodulation session; D) clinical presentation after the 7
th
photobiomodulation session.
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Volume 31 - N. 1
Laser Therapy 23
reabsorption of superoxide anions by mitochondria
16
and v) the NO hypothesis that laser irradiation could
reverse the partial inhibition of the catalytic center by
NO and ultimately increase the rate of binding and res-
piration by O2.
17
While the secondary mechanisms of
PBM include the activation of different intracellular
signaling pathways, they regulate nucleic acid and pro-
tein synthesis, enzyme activation, cell cycle progression,
and various transcription factors.
18
The activation of
these primary and secondary factors is responsible for
the so-called tertiary effect that is linked to cell prolif-
eration and migration and protein synthesis is respon-
sible for the systemic effect.
18
Still, it is known that the
EM pathogenesis pathway suggests a trigger of autore-
active T cells by viral cells (HSV). Inflammatory re-
sponses are initiated by the recruitment of CD4+
T-helper 1 (Th1) cells.
19
Interferon-gamma (IFN-y)
generated by this response upregulates cytokines and
chemokines that amplify cutaneous inflammatory
events, with an increase in circulating leukocytes,
monocytes, natural killer (NK) cells, and autoreactive
T cells to the epidermis.
19
Thus, PBM may be promis-
ing as an anti-inflammatory agent and reduce these and
other components in autoimmune diseases, as seen in
the present case. Furthermore, it offers a unique ap-
proach as it is non-invasive and without side effects, as
autoimmune diseases are treated with corticosteroids
that have a multitude of undesirable systemic con-
sequences.
20
However, it is worth mentioning that the
complete understanding of the pathogenesis of EM and
the effects of PBM in autoimmune diseases is not clear,
making it impossible to understand the mechanism of
action of PBM in MS.
In summary, our case emphasizes the treatment of EM
of the oral mucosa with LLLT and how much there was
a significant clinical improvement with the use of PBM.
However, it is important to emphasize that there is a lack
of scientific evidence regarding the pathogenesis of EM
and the effects of PBM in autoimmune diseases. The
present case report presents a possibility for future inves-
tigations of LLLT as a treatment of autoimmune diseases
with oral or systemic presentation.
Conflict of interest: the authors have no conflict of in-
terest to declare.
Funding: this study was not supported by any funding.
Conflict of interest: the authors declare that they have
no conflict of interest.
Ethical approval: all procedures performed in studies in-
volving human participants were in accordance with the
ethical standards of the institutional and/or national re-
search committee and with the 1964 Helsinki Declara-
tion and its later amendments or comparable ethical
standards.
Consent for publication: consent for publication was
obtained for every person’s data included in the study.
Availability of data and materials: all data generated or
analyzed during this study are included in this published
article.
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